Human chorionic gonadotropin (“hCG”) is a heterodimeric placental glycoprotein hormone required in pregnancy. In the urine of human pregnancy and in commercial hCG preparations, it occurs in a variety of forms, including breakdown products. Several investigators have studied the effects of heterodimeric hCG and its variants on the immune system because of their putative role in preventing the rejection of the fetal allograft during pregnancy. Several reports have suggested modulation of the immune system by intact hormone, but such effects of breakdown products have not been reported.
Khan et al., Hum Immunol. 2002 January; 63(1):1-7, reported inhibition of septic shock in mice by a 6-mer oligopeptide (VLPALP (SEQ ID NO:6)) derived from the beta-chain of human chorionic gonadotropin hormone. A single treatment with this hexapeptide after high dose lipopolysaccharide (“LPS”) injection inhibited septic shock in mice. Benner and Khan (Scand J Immunol. 2005 July; 62 Suppl 1:62-6) studied the possible immunological activity of the in vivo liberated peptide fragments originating from nicking of the sequence MTRVLQGVLPALPQVVC (residues 41-57) of loop 2 of the beta-subunit of hCG (SEQ ID NO:7). It is there reported that several of 3-7 amino acid-long peptides taken from loop 2 of the beta-subunit—and alanine-replacement peptides derived of some—displayed significant anti-inflammatory activity as measured by the inhibition of septic shock syndrome in mice. Selection was based on the known preferential cleavage sites of the sequence MTRVLQGVLPALPQVVC (residues 41-57) of loop 2 of the beta-subunit of hCG (SEQ ID NO:7).
(Cole et al., J Clin Endocr Metab 1993; 76:704-710; Alfthan H, Stenman U H. Mol Cell Endocrinol 1996; 125:107-120; Kardana A, et al., Endocrinology 1991; 129:1541-1550; Cole et al., Endocrinology 1991; 129:1559-1567; Birken S, Maydelman Y, Gawinowicz M A. Methods 2000; 21:3-14) The peptides LQGV (SEQ ID NO:3) and AQGV (SEQ ID NO:2) were selected for synthesis, of which the results are presented here.